Genetic Variant ALOX5:c.-180_-175delGCGGGG (chr10-45374099-TGCGGGG-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_000698.5(ALOX5):c.-180_-175delGCGGGG variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.103 in 821,412 control chromosomes in the GnomAD database, including 6,828 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.16 ( 2090 hom., cov: 22)

Exomes 𝑓: 0.089 ( 4738 hom. )

Consequence

ALOX5
NM_000698.5 upstream_gene

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.450

Publications

13 publications found

Variant links:

Genes affected

ALOX5 (HGNC:435): (arachidonate 5-lipoxygenase) This gene encodes a member of the lipoxygenase gene family and plays a dual role in the synthesis of leukotrienes from arachidonic acid. The encoded protein, which is expressed specifically in bone marrow-derived cells, catalyzes the conversion of arachidonic acid to 5(S)-hydroperoxy-6-trans-8,11,14-cis-eicosatetraenoic acid, and further to the allylic epoxide 5(S)-trans-7,9-trans-11,14-cis-eicosatetrenoic acid (leukotriene A4). Leukotrienes are important mediators of a number of inflammatory and allergic conditions. Mutations in the promoter region of this gene lead to a diminished response to antileukotriene drugs used in the treatment of asthma and may also be associated with atherosclerosis and several cancers. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

ALOX5 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.206 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALOX5	NM_000698.5 link	c.-180_-175delGCGGGG		upstream_gene_variant		ENST00000374391.7	NP_000689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALOX5	ENST00000374391.7 link	c.-180_-175delGCGGGG		upstream_gene_variant		1	NM_000698.5	ENSP00000363512.2
ALOX5	ENST00000542434.5 link	c.-180_-175delGCGGGG		upstream_gene_variant		1		ENSP00000437634.1

Frequencies

GnomAD3 genomes

AF:

0.164

AC:

24617

AN:

149816

Hom.:

2086

Cov.:

show subpopulations

Gnomad AFR

AF:

0.160

Gnomad AMI

AF:

0.218

Gnomad AMR

AF:

0.132

Gnomad ASJ

AF:

0.165

Gnomad EAS

AF:

0.216

Gnomad SAS

AF:

0.197

Gnomad FIN

AF:

0.193

Gnomad MID

AF:

0.161

Gnomad NFE

AF:

0.163

Gnomad OTH

AF:

0.168

GnomAD4 exome

AF:

0.0894

AC:

60028

AN:

671494

Hom.:

4738

AF XY:

0.0926

AC XY:

30120

AN XY:

325374

show subpopulations

African (AFR)

AF:

0.110

AC:

1460

AN:

13326

American (AMR)

AF:

0.102

AC:

724

AN:

7112

Ashkenazi Jewish (ASJ)

AF:

0.136

AC:

1457

AN:

10708

East Asian (EAS)

AF:

0.197

AC:

4223

AN:

21384

South Asian (SAS)

AF:

0.131

AC:

1664

AN:

12716

European-Finnish (FIN)

AF:

0.197

AC:

4070

AN:

20644

Middle Eastern (MID)

AF:

0.0928

AC:

194

AN:

2090

European-Non Finnish (NFE)

AF:

0.0776

AC:

43065

AN:

554902

Other (OTH)

AF:

0.111

AC:

3171

AN:

28612

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

2336

4672

7008

9344

11680

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1082

2164

3246

4328

5410

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.164

AC:

24644

AN:

149918

Hom.:

2090

Cov.:

AF XY:

0.166

AC XY:

12138

AN XY:

73096

show subpopulations

African (AFR)

AF:

0.160

AC:

6553

AN:

40948

American (AMR)

AF:

0.131

AC:

1995

AN:

15172

Ashkenazi Jewish (ASJ)

AF:

0.165

AC:

567

AN:

3446

East Asian (EAS)

AF:

0.217

AC:

1045

AN:

4824

South Asian (SAS)

AF:

0.197

AC:

925

AN:

4696

European-Finnish (FIN)

AF:

0.193

AC:

1992

AN:

10310

Middle Eastern (MID)

AF:

0.174

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.163

AC:

10977

AN:

67268

Other (OTH)

AF:

0.167

AC:

348

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.482

Heterozygous variant carriers

931

1862

2794

3725

4656

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

272

544

816

1088

1360

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0537

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.45

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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10-45374099-TGCGGGGGCGGGGGCGGGGGCGGGG-TGCGGGGGCGGGGGCGGGG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over